Pyridine → (3RS,4SR)-3-[(SR)-1-(5-Cyano-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidine-1-carbonyl chloride

HRID 1158666Notes

Reaction equation

HRID 1158666 reaction equation
ClC(Cl)(OC(=O)[O:6][C:7]([Cl:10])(Cl)Cl)Cl.[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]2[CH2:25][NH:24][CH2:23][CH:22]2[CH:26]([O:28][C:29]2[CH:36]=[CH:35][C:32]([C:33]#[N:34])=[CH:31][N:30]=2)[CH3:27])[CH:17]=[CH:18][C:19]=1[Cl:20].N1C=CC=CC=1.CCOC(C)=O>C(Cl)Cl>[C:33]([C:32]1[CH:35]=[CH:36][C:29]([O:28][CH:26]([CH:22]2[CH:21]([C:16]3[CH:17]=[CH:18][C:19]([Cl:20])=[C:14]([Cl:13])[CH:15]=3)[CH2:25][N:24]([C:7]([Cl:10])=[O:6])[CH2:23]2)[CH3:27])=[N:30][CH:31]=1)#[N:34]

Participants

6

Reactant 4

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 94429TriphosgeneHCID 669997186-{(SR)-1-[(3RS,4SR)-4-(3,4-Dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile

Product 1

HCID 86628181(3RS,4SR)-3-[(SR)-1-(5-Cyano-pyridin-2-yloxy)-ethyl]-4-(3,4-dichloro-phenyl)-pyrrolidine-1-carbonyl chlorideYield 154.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of carbonic acid ditrichloromethyl ester (triphosgene) (67 mg, 0.22 mmol) in CH2Cl2 (14 ml) at −78° C., was added a solution of 6-{(SR)-1-[(3RS,4SR)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-ethoxy}-nicotinonitrile (intermediate XV-B-4) (210 mg, 0.56 mmol) and pyridine (0.10 ml, 1.23 mmol) in CH2Cl2 (7 mL) over 30 minutes. The temperature was raised to RT, and stirring was continued over night. The organic phase was washed with H2O, dried over Na2SO4. Concentration under vacuo yielded and column chromatography (SiO2, EtOAc/H, 1:1) yielded 144 mg (57%) of the title compound as a viscous colorless oil.

Workup

  1. waitwas continued over night
  2. washThe organic phase was washed with H2O
  3. dry with materialdried over Na2SO4
  4. concentrationConcentration under vacuo
  5. customyielded

Sources & evidence

ORD record
ord-71cecf491bd049c5b9a2674e2e3c1815
Source dataset
uspto-grants-2010_10
Patent number
US07812021B2

Reaction notes

Loading…